Co-culture of chondrocytes and stem cells: a review of head and neck cell lines for cartilage regeneration.

INTRODUCTION: Bioprinting, using "bio-inks" consisting of living cells, supporting structures and biological motifs to create customized constructs, is an emerging technique that aims to overcome the challenges of cartilaginous reconstruction of head and neck structures. Several living cell lines and culturing methods have been explored as bio-inks with varying efficacy. Co-culture of primary chondrocytes and stem cells (SCs) is one technique, well established for degenerative joint disease treatment, with potential for use in expanding chondrocyte populations for bio-inks. This study aims to evaluate the techniques for co-culture of primary chondrocytes and SCs for head and neck cartilage regeneration. METHODS: A literature review was performed through OVID/Web of Science/MEDLINE/BIOSIS Previews/Embase. Studies reporting on chondrocytes and SCs in conjunction with co-culture or cartilage regeneration were included. Studies not reporting on findings from chondrocytes/SCs of the head and neck were excluded. Extracted data included cell sources, co-culture ratios and histological, biochemical and clinical outcomes. RESULTS: 15 studies met inclusion criteria. Auricular cartilage was the most common chondrocyte source (n=10), then nasal septum (n=5), articular (n=1) and tracheal cartilage (n=1). Bone marrow was the most common SC source (n=9) then adipose tissue (n=7). Techniques varied, with co-culture ratios ranging from 1:1 to 1:10. All studies reported co-culture to be superior to SC mono-culture by all outcomes. Most studies reported superiority or equivalence of co-culture to chondrocyte mono-culture by all outcomes. When comparing clinical outcomes, co-culture constructs were equivalent to chondrocyte mono-culture in diameter, and equivalent or inferior in wet weight and height. CONCLUSION: Co-culture of primary chondrocytes and SCs is a promising technique for expanding chondrocyte populations, with at least equivalence to chondrocyte mono-culture and superior to SC mono-culture when seeded at the same chondrocyte densities. However, there remains a lack of consensus regarding the optimal cell sources and co-culture ratios.

Performance of personalised prosthesis under static pressure: Numerical analysis and experimental validation.

This study investigates the performance of personalised middle ear prostheses under static pressure through a combined approach of numerical analysis and experimental validation. The sound transmission performances of both normal and reconstructed middle ears undergo changes under high positive or negative pressure within the middle ear cavity. This pressure fluctuation has the potential to result in prosthesis displacement/extrusion in patients. To optimise the design of middle ear prostheses, it is crucial to consider various factors, including the condition of the middle ear cavity in which the prosthesis is placed. The integration of computational modelling techniques with non-invasive imaging modalities has demonstrated significant promise and distinct prospects in middle ear surgery. In this study, we assessed the efficacy of Finite Element (FE) analysis in modelling the responses of both normal and reconstructed middle ears to elevated static pressure within the ear canal. The FE model underwent validation using experimental data derived from human cadaveric temporal bones before progressing to subsequent investigations. Afterwards, we assessed stapes and umbo displacements in the reconstructed middle ear under static pressure, with either a columella-type prosthesis or a prosthetic incus, closely resembling a healthy incus. Results indicated the superior performance of the prosthetic incus in terms of both sound transmission to the inner ear and stress distribution patterns on the TM, potentially lowering the risk of prosthesis displacement/extrusion. This study underscores the potential of computational analysis in middle ear surgery, encompassing aspects such as prosthesis design, predicting outcomes in ossicular chain reconstruction (OCR), and mitigating experimental costs.

The Impact of Polycystic Ovary Syndrome (PCOS) on the Risk of Developing Ovarian Cancer and Thyroid Disorders: A Comprehensive Review.

Polycystic ovary syndrome (PCOS) is a common hormonal disorder that affects women. It is characterized by hyperandrogenism, polycystic ovarian morphology, and other related disorders. It is associated with various health conditions, such as infertility and increased risk of heart problems. Ovarian cancer is also a significant concern, as it is the fifth leading cause of death in women. While there is evidence suggesting a potential association between PCOS and ovarian cancer, the exact nature of this relationship remains unclear. Thyroid disorders, particularly hypothyroidism and Hashimoto's thyroiditis, have also been linked to PCOS. The presence of hypothyroidism can contribute to the development of polycystic ovarian morphology, affecting ovulation and hormone balance. Many works have shown a higher ubiquity of autoimmune thyroid disease in PCOS patients, indicating a potential association between the two conditions. The occurrence of PCOS, hirsutism, and acne underscores the frequency of endocrine disorders in women. This review paper examines the present relevant work on the association between PCOS and ovarian cancer as well as PCOS and thyroid disorders. A systematic literature search was conducted on PubMed, such as PubMed, Scopus, and Google Scholar database, to identify peer-reviewed publications pertaining to PCOS, ovarian cancer, and thyroid disorders. While some studies have delineated a significant link between PCOS and ovarian cancer or thyroid disorders, others have yielded inconclusive results. Further research is necessary to establish a definitive causal relationship between these conditions. Understanding the relationship between PCOS, ovarian cancer, and thyroid disorders is crucial for early detection, accurate diagnosis, and effective management of these conditions. Identifying potential risk factors and developing appropriate screening strategies can improve women's health outcomes and reduce the burden associated with these disorders.

Clinical application of 3-dimensional tissue volume assessment using CloudCompare.

Adjunctive procedures, including autologous fat grafting and surgical debulking, may be required to optimise facial contours following maxillomandibular reconstruction. A standardised method for the quantitative analysis of volumetric change and the impact of restoration of facial symmetry on health-related quality of life remains unclear. We use two case studies to illustrate the value of a combination of objective 3-dimenmsional (3D) measurements, clinical assessments, and patient-reported outcomes, using the FACE-Q questionnaire to elucidate the benefits of adjunctive procedures.

Meniere's disease: Pathogenesis, treatments, and emerging approaches for an idiopathic bioenvironmental disorder.

Meniere's disease (MD) is a severe inner ear condition known by debilitating symptoms, including spontaneous vertigo, fluctuating and progressive hearing loss, tinnitus, and aural fullness or pressure within the affected ear. Prosper Meniere first described the origins of MD in the 1860s, but its underlying mechanisms remain largely elusive today. Nevertheless, researchers have identified a key histopathological feature called Endolymphatic Hydrops (ELH), which refers to the excessive buildup of endolymph fluid in the membranous labyrinth of the inner ear. The exact root of ELH is not fully understood. Still, it is believed to involve several biological and bioenvironmental etiological factors such as genetics, autoimmunity, infection, trauma, allergy, and new theories, such as saccular otoconia blocking the endolymphatic duct and sac. Regarding treatment, there are no reliable and definitive cures for MD. Most therapies focus on managing symptoms and improving the overall quality of patients' life. To make significant advancements in addressing MD, it is crucial to gain a fundamental understanding of the disease process, laying the groundwork for more effective therapeutic approaches. This paper provides a comprehensive review of the pathophysiology of MD with a focus on old and recent theories. Current treatment strategies and future translational approaches (with low-level evidence but promising results) related to MD are also discussed, including patents, drug delivery, and nanotechnology, that may provide future benefits to patients suffering from MD.

Different levels of arsenic exposure through cooked rice and its associated benefit-risk assessment from rural and urban populations of West Bengal, India: a probabilistic approach with sensitivity analysis.

Rice arsenic (As) contamination and its consumption poses a significant health threat to humans. The present study focuses on the contribution of arsenic, micronutrients, and associated benefit-risk assessment through cooked rice from rural (exposed and control) and urban (apparently control) populations. The mean decreased percentages of As from uncooked to cooked rice for exposed (Gaighata), apparently control (Kolkata), and control (Pingla) areas are 73.8, 78.5, and 61.3%, respectively. The margin of exposure through cooked rice (MoEcooked rice) < 1 signifies the existence of health risk for all the studied exposed and control age groups. The respective contributions of iAs (inorganic arsenic) in uncooked and cooked rice are nearly 96.6, 94.7, and 100% and 92.2, 90.2, and 94.2% from exposed, apparently control, and control areas. LCR analysis for the exposed, apparently control, and control populations (adult male: 2.1 × 10-3, 2.8 × 10-4, 4.7 × 10-4; adult female: 1.9 × 10-3, 2.1 × 10-4, 4.4 × 10-4; and children: 5.8 × 10-4, 4.9 × 10-5, 1.1 × 10-4) through cooked rice is higher than the recommended value, i.e., 1 × 10-6, respectively, whereas HQ > 1 has been observed for all age groups from the exposed area and adult male group from the control area. Adults and children from rural area showed that ingestion rate (IR) and concentration are the respective influencing factors towards cooked rice As, whereas IR is solely responsible for all age groups from urban area. A vital suggestion is to reduce the IR of cooked rice for control population to avoid the As-induced health risks. The average intake (µg/day) of micronutrients is in the order of Zn > Se for all the studied populations and Se intake is lower for the exposed population (53.9) compared to the apparently control (140) and control (208) populations. Benefit-risk assessment supported that the Se-rich values in cooked rice are effective in avoiding the toxic effect and potential risk from the associated metal (As).

Otosclerosis: audiometric results and quality of life after stapedectomy with interposition or CO2 laser-calibrated stapedotomy without interposition.

BACKGROUND: The surgical treatment of otosclerosis consists of the replacement of the stapes using a piston. AIMS/OBJECTIVES: The objective of this study is to assess the audiometric results and quality of life (QOL) of patients who underwent surgery for otosclerosis by stapedectomy with fascia interposition (STIP) or by stapedotomy using CO2 laser (SLaser) without fascia interposition. MATERIAL AND METHODS: Ninety-one patients operated on for otosclerosis by STIP (40 patients) and by SLaser (51 patients) were included. Audiometric results were graphically displayed using the Amsterdam Hearing Evaluation Plot and were compared to the Common Otology Database (COD) comprising 660 patients. The patients' QOL was assessed with an otological validated survey. The significance level was p < .05. RESULTS: There was no significant difference in hearing improvement between SLaser and STIP-operated patients. There was no significant difference between our results and that of COD. QOL was significantly improved (+3.5/10) postoperatively for both STIP and SLaser in both social and professional fields. CONCLUSIONS AND SIGNIFICANCE: By comparing QOL and hearing gain of STIP and SLaser, our results suggest that both surgical techniques are a safe and successful treatment for otosclerotic stapes fixation. Further studies aiming at comparing larger series may confirm and refine these results.

Virtual reality digital surgical planning for jaw reconstruction: a usability study.

BACKGROUND: Digital surgical planning (DSP) has revolutionized the preparation and execution of the management of complex head and neck pathologies. The addition of virtual reality (VR) allows the surgeon to have a three-dimensional experience with six degrees of freedom for visualizing and manipulating objects. This pilot study describes the participants experience with the first head and neck reconstructive VR-DSP platform. METHODS: An original VR-DSP platform has been developed for planning the ablation and reconstruction of head and neck pathologies. A prospective trial utilizing this platform involving reconstructive surgeons was performed. Participants conducted a simulated VR-DSP planning session, pre- and post-questionnaire as well as audio recordings allowing for qualitative analysis. RESULTS: Thirteen consultant reconstructive surgeons representing three surgical backgrounds with varied experience were recruited. The majority of surgeons had no previous experience with VR. Based on the system usability score, the VR-DSP platform was found to have above average usability. The qualitative analysis demonstrated the majority had a positive experience. Participants identified some perceived barriers to implementing the VR-DSP platform. CONCLUSIONS: Virtual reality-digital surgical planning is usable and acceptable to reconstructive surgeons. Surgeons were able to perform the steps in an efficient time despite limited experience. The addition of VR offers additional benefits to current VSP platforms. Based on the results of this pilot study, it is likely that VR-DSP will be of benefit to the reconstructive surgeon.

Hydrogel: A Potential Material for Bone Tissue Engineering Repairing the Segmental Mandibular Defect.

Free flap surgery is currently the only successful method used by surgeons to reconstruct critical-sized defects of the jaw, and is commonly used in patients who have had bony lesions excised due to oral cancer, trauma, infection or necrosis. However, donor site morbidity remains a significant flaw of this strategy. Various biomaterials have been under investigation in search of a suitable alternative for segmental mandibular defect reconstruction. Hydrogels are group of biomaterials that have shown their potential in various tissue engineering applications, including bone regeneration, both through in vitro and in vivo pre-clinical animal trials. This review discusses different types of hydrogels, their fabrication techniques, 3D printing, their potential for bone regeneration, outcomes, and the limitations of various hydrogels in preclinical models for bone tissue engineering. This review also proposes a modified technique utilizing the potential of hydrogels combined with scaffolds and cells for efficient reconstruction of mandibular segmental defects.

Effect of Radiotherapy on Functional and Health-Related Quality of Life Outcomes after Jaw Reconstruction.

Long-term health-related quality of life (HRQOL) and functional outcomes following mandibular and maxillary reconstruction are lacking. To determine these outcomes, a cross-sectional study of patients with a history of cancer who underwent jaw reconstruction was undertaken. Participants were identified from a database of jaw reconstruction procedures at the Chris O'Brien Lifehouse (Sydney, Australia). Eligible patients had at least one month follow-up, were aged ≥18 years at surgery, and had history of malignancy. HRQOL was measured using the FACE-Q Head and Neck Cancer Module (FACE-Q H&N). Functional outcomes were measured using the FACE-Q H&N, MD Anderson Dysphagia Inventory (MDADI) and Speech Handicap Index (SHI). Ninety-seven questionnaires were completed (62% response rate). Mean age of respondents was 63.7 years, 61% were male, and 64% underwent radiotherapy. Treatment with radiotherapy was associated with worse outcomes across 10/14 FACE-Q H&N scales, three MDADI subscales and one composite score, and the SHI. Mean differences in scores between irradiated and non-irradiated patients exceeded clinically meaningful differences for the MDADI and SHI. Issues with oral competence, saliva, speaking, and swallowing worsened with increasing time since surgery. Younger patients reported greater concerns with appearance, smiling, speaking, and cancer worry. Women reported greater concerns regarding appearance and associated distress. History of radiotherapy substantially impacts HRQOL and function after jaw reconstruction. Age at surgery and gender were also predictors of outcomes and associated distress. Pre-treatment counselling of patients requiring jaw reconstruction may lead to improved survivorship for patients with head and neck cancer.

Potential nanotechnology-based diagnostic and therapeutic approaches for Meniere's disease.

Meniere's disease (MD) is a progressive inner ear disorder involving recurrent and prolonged episodes or attacks of vertigo with associated symptoms, resulting in a significantly reduced quality of life for sufferers. In most cases, MD starts in one ear; however, in one-third of patients, the disorder progresses to the other ear. Unfortunately, the etiology of the disease is unknown, making the development of effective treatments difficult. Nanomaterials, including nanoparticles (NPs) and nanocarriers, offer an array of novel diagnostic and therapeutic applications related to MD. NPs have specific features such as biocompatibility, biochemical stability, targetability, and enhanced visualization using imaging tools. This paper provides a comprehensive and critical review of recent advancements in nanotechnology-based diagnostic and therapeutic approaches for MD. Furthermore, the crucial challenges adversely affecting the use of nanoparticles to treat middle ear disorders are investigated. Finally, this paper provides recommendations and future directions for improving the performances of nanomaterials on theragnostic applications of MD.

Insights into Inner Ear Function and Disease Through Novel Visualization of the Ductus Reuniens, a Seminal Communication Between Hearing and Balance Mechanisms.

The sensory end-organs responsible for hearing and balance in the mammalian inner ear are connected via a small membranous duct known as the ductus reuniens (also known as the reuniting duct (DR)). The DR serves as a vital nexus linking the hearing and balance systems by providing the only endolymphatic connection between the cochlea and vestibular labyrinth. Recent studies have hypothesized new roles of the DR in inner ear function and disease, but a lack of knowledge regarding its 3D morphology and spatial configuration precludes testing of such hypotheses. We reconstructed the 3D morphology of the DR and surrounding anatomy using osmium tetroxide micro-computed tomography and digital visualizations of three human inner ear specimens. This provides a detailed, quantitative description of the DR's morphology, spatial relationships to surrounding structures, and an estimation of its orientation relative to head position. Univariate measurements of the DR, inner ear, and cranial planes were taken using the software packages 3D Slicer and Zbrush. The DR forms a narrow, curved, flattened tube varying in lumen size, shape, and wall thickness, with its middle third being the narrowest. The DR runs in a shallow bony sulcus superior to the osseus spiral lamina and adjacent to a ridge of bone that we term the "crista reuniens" oriented posteromedially within the cranium. The DR's morphology and structural configuration relative to surrounding anatomy has important implications for understanding aspects of inner ear function and disease, particularly after surgical alteration of the labyrinth and potential causative factors for Ménière's disease.

Facial nerve palsy: Narrative review on the importance of the eye and its assessment.

New solutions are emerging that address specific facial regions in facial nerve palsy (FNP). However the most dreaded consequence of FNP is paralytic lagophthalmos threatening the eye. A way to prioritize these regions is thus required. A review of the literature is conduced to capture the current concepts in evaluating FNP. Overall, patients are assessed from three perspectives: from the clinician's perspective using validated clinician-based grading instruments, from patient's perspective based on FNP-specific patient-reported outcome measures, and from the perspective of the layperson. The existing tools however provide limited information regarding the relative importance of different regions of the face. The eye appears to be an area of great concern for the patient where most surgical therapies are directed at. Addressing ocular problems in FNP carry a high priority but this is not clearly reflected by the standard systems.

Bioprinting of Chondrocyte Stem Cell Co-Cultures for Auricular Cartilage Regeneration.

Advances in 3D bioprinting allows not only controlled deposition of cells or cell-laden hydrogels but also flexibility in creating constructs that match the anatomical features of the patient. This is especially the case for reconstructing the pinna (ear), which is a large feature of the face and made from elastic cartilage that primarily relies on diffusion for nutrient transfer. The selection of cell lines for reconstructing this cartilage becomes a crucial step in clinical translation. Chondrocytes and mesenchymal stem cells are both studied extensively in the area of cartilage regeneration as they are capable of producing cartilage in vitro. However, such monoculture systems involve unfavorable processes and produce cartilage with suboptimal characteristics. Co-cultures of these cell types are known to alleviate these limitations to produce synergically active chondrocytes and cartilage. The current study utilized a 3D bioprinted scaffold made from combined gelatine methacryloyl and methacrylated hyaluronic acid (GelMA/HAMA) to interrogate monocultures and co-cultures of human septal chondrocytes (primary chondrocytes, PCs) and human bone marrow-derived mesenchymal stem cells (BM-hMSCs). This study is also the first to examine co-cultures of healthy human chondrocytes with human BM-hMSCs encapsulated in GelMA/HAMA bioprinted scaffolds. Findings revealed that the combination of MSCs and PCs not only yielded cell proliferation that mimicked MSCs but also produced chondrogenic expressions that mimicked PCs. These findings suggested that co-cultures of BM-hMSCs and healthy septal PCs can be employed to replace monocultures in chondrogenic studies for cartilage regeneration in this model. The opportunity for MSCs used to replace PCs alleviates the requirement of large cartilage biopsies that would otherwise be needed for sufficient cell numbers and therefore can be employed for clinical applications.

"Surgical technique: A novel pedicled periosteal scapular flap to facilitate bone growth in an Ovine model".

BACKGROUND: Vascularised periosteum can used for reconstructing bony defects due to its intrinsic osteogenic properties. This osteogenic potential can be harnessed as a vascularised flap to induce bone growth of complex constructs in-vivo. The authors aimed to use a novel pedicled periosteal flap from the scapula to induce bone growth in a critical sized construct. METHODS: Eight sheep were used as live animal models. A novel periosteal flap was raised from the infraspinous fossa of each animal and wrapped around non-vascularised autologous bone graft. The constructs were allowed to incubate between 1 and 84 days before harvest. Analysis of the flap was done via histopathology using haematoxylin and eosin staining. RESULTS: All flaps were viable at the conclusion of surgery. Seven flaps showed variable thickening with matrix deposition. One flap was devitalised at time of harvest. CONCLUSION: The novel periosteal scapular flap described is a promising technique to induce bone growth in complex constructs.

Health-related quality of life in maxillectomy patients undergoing dentoalveolar rehabilitation.

OBJECTIVES: Surgical resection of the maxilla impairs aesthetics, speech, swallowing, and mastication. Maxillary reconstruction is increasingly performed with virtual surgical planning (VSP) to enhance functional dental rehabilitation with a conventional denture or osseointegrated implants. The aim of this study was to determine whether dental status and VSP is associated with health-related quality of life (HRQOL) and function in patients who have undergone maxillectomy. MATERIALS AND METHODS: A cross-sectional study was conducted among patients who underwent free flap reconstruction or obturation of the maxilla between July 2009 and December 2020. The FACE-Q Head and Neck Cancer (FACE-Q) module, M.D. Anderson Dysphagia Inventory (MDADI), and Speech Handicap Index (SHI) were used to evaluate HRQOL. RESULTS: Forty-three patients (response rate 59%) completed questionnaires and 48% underwent dental rehabilitation. In Okay Class II and III defects, adjusting for the effect of radiotherapy and time from surgery, there was a positive association between denture status and FACE-Q smiling (p = 0.020), eating (p = 0.012), smiling (p = 0.015), and MDADI global (p = 0.015), emotional (p = 0.027), functional (p = 0.028), and composite (p = 0.029) scores. VSP was associated with FACE-Q swallowing (p = 0.005), drooling (p = 0.030), eating (p = 0.008), smiling (p = 0.021), MDADI global (p = 0.017), emotional (p = 0.041), functional (p = 0.040), composite (p = 0.038), and SHI total scores (p = 0.042). CONCLUSIONS: Dentoalveolar rehabilitation and VSP were associated with higher HRQOL scores relating to eating and drinking, smiling, and speaking.

Anatomy of the lateral orbital wall: A topographic investigation for identification of the lateral canthal attachment.

BACKGROUND: There is a growing effort to develop implantable bionics for restoring eye closure in paralytic lagophthalmos. Knowledge of the natural eyelid attachments is important for active implants that mobilise these attachments or replace them with a sling. Whitnall's tubercle (WT) is traditionally used to identify lateral canthal attachments; however, it is not always present. This study seeks an alternative means of identifying the insertion of the lateral canthus to aid the application of bionic implants. METHODS: Complete CT head scans of patients in the Sydney Head and Neck Cancer Institute database were retrieved for analysis. The CT scans were segmented using bone and soft-tissue thresholding and then reconstructed. The location of WT and the lateral canthal insertion were recorded and their relation to key anatomical landmarks assessed. RESULTS: Ninety orbits from 45 complete head scans were analysed. WT could be identified bilaterally in 18/45 (40%) samples. The average distance from WT to zygomaticofrontal suture and to lateral orbital margin was 10.8 ±â€¯0.4 mm and 4.4 ±â€¯0.2 mm, respectively. The average height of the lateral canthal insertion from the Jugale point was 13.9 ±â€¯1.8 mm. On regression analysis, the height of lateral canthal insertion was strongly predicted by the height of lateral orbital wall as the determined by the maximum distance of the ZFS from the Jugale point (p = <0.001). CONCLUSION: In the absence of WT, the height of the lateral orbital wall can be reliability used to localise the insertion site of the lateral canthus.